Back to resultsGrapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
Primary Purpose
Non-small Cell Lung Cancer Adenocarcinoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
grapiprant and pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer Adenocarcinoma
Eligibility Criteria
Key Inclusion Criteria:
- Male and female adult patients at least 18 years of age on day of signing informed consent
- Histologically confirmed non-small cell lung cancer (NSCLC) adenocarcinoma
- Advanced (stage IIIb) disease that is not amenable to curative intent treatment with concurrent chemoradiation and metastatic (stage IV) patients
- Progressed clinically and/or radiographically per RECIST v1.1 after receiving a PD-1 or PD-L1 antagonist for a minimum of 12 weeks
- Measurable disease per RECIST v1.1
- Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy for multiple core biopsies and participant is willing to provide tissue from newly obtain biopsies on study in a subgroup of patients
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Adequate organ function
- Highly effective birth control
- Able to swallow and absorb oral tablets
Key Exclusion Criteria:
- Current use of NSAIDs, COX-2 inhibitors
- Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration
- No history of smoking (≤100 cigarettes lifetime)
- History of severe hypersensitivity reactions to a PD-1/L1 antibody
- Received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment or 5 half-lives, whichever is shorter
- Received prior radiotherapy within 2 weeks of start of study treatment
- Has received a live vaccine within 30 days prior to the first dose of study treatment
- Taking strong CYP3A4 or P-glycoprotein inhibitors or inducers
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Known additional malignancy that is progressing or has required active treatment within the past 3 years (with some permitted exceptions)
- Known active CNS metastases and/or carcinomatous meningitis
- Active autoimmune disease that has required systemic treatment in past 2 years
- History of pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Recent or current GI ulcer, colitis or non-immune colitis
- Known history of human immunodeficiency virus (HIV) infection, or known active Hepatitis B, or Hepatitis C virus infection
- Has had an allogeneic tissue/solid organ transplant
- Clinically significant (i.e.active) cardiovascular disease
Sites / Locations
- Stanford University Medical Center
- Barbara Ann Karmanos Cancer Institute
- START Midwest
- University of Pennsylvania Abramson Cancer Center
- Fox Chase Cancer Center
- Virginia Cancer Specialists
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
grapiprant and pembrolizumab combination
Arm Description
Participants will be treated with grapiprant in combination with pembrolizumab.
Outcomes
Primary Outcome Measures
Safety and tolerability of grapiprant in combination with pembrolizumab
Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0
Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
Objective response rate (ORR)
Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
Secondary Outcome Measures
Progression-free survival (PFS)
Participants who discontinue treatment without disease progression
Overall survival (OS)
Date of study drug to date of death due to any cause
Duration of treatment (DoT)
Disease response for time of duration on treatment
Disease control rate (DCR)
Percentage of patients who have achieved CR, PR and stable disease
Duration of response (DoR)
Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
PK of grapiprant: AUC
Area under the plasma concentration-time curve
PK of grapiprant: Cmax
Peak serum concentration of grapiprant
Plasma decay half-life (t1/2)
Measurement of half-life of grapiprant after dosing
Apparent oral clearance (CL/F)
Rate of elimination of the drug from plasma after oral administration
Peak to trough ratio
Measure how drug effect is sustained over dose interval
Observed accumulation ratio
Relationship between the dosing interval and the rate of elimination for the drug
Pharmacodynamic immune effects in paired tumor biopsies
Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment
Full Information
NCT ID
NCT03696212
First Posted
October 3, 2018
Last Updated
February 19, 2021
Sponsor
Arrys Therapeutics
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT03696212
Brief Title
Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
Official Title
Open Label, Single Arm, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Based on the totality of the generated combined safety and efficacy data in the interim period, the company decided to terminate the combination study in NSCLC patients. There are no subjects on study drug at this time or in the EOT Follow-up period.
Study Start Date
January 8, 2019 (Actual)
Primary Completion Date
February 15, 2021 (Actual)
Study Completion Date
February 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrys Therapeutics
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will be conducted in adult participants diagnosed with NSCLC who have been previously treated for a minimum of 12 weeks with any PD-1 or PD-L1 checkpoint inhibitor. This is a phase 1b/2, multi-center, open label study designed to assess safety and tolerability of grapiprant in combination with pembrolizumab, to determine the recommended phase 2 dose (RP2D) with pembrolizumab, and to evaluate disease response with grapiprant based on investigator assessments. Pharmacokinetics, pharmacodynamics and response biomarkers will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
grapiprant and pembrolizumab combination
Arm Type
Experimental
Arm Description
Participants will be treated with grapiprant in combination with pembrolizumab.
Intervention Type
Drug
Intervention Name(s)
grapiprant and pembrolizumab
Other Intervention Name(s)
ARYS-007, MK-3475, KEYNOTE-888, IK-007
Intervention Description
Participants will be administered 21-day cycles of oral grapiprant in combination with IV pembrolizumab
Primary Outcome Measure Information:
Title
Safety and tolerability of grapiprant in combination with pembrolizumab
Description
Number of incidence, severity, relationship, concomitant medications administered, and duration of treatment emergent adverse events using CTCAE v5.0
Time Frame
Up to 90 days after the end of treatment (average of 7 months)
Title
Define the recommended phase 2 dose (RP2D) of grapiprant combined with pembrolizumab
Description
Number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0
Time Frame
Through Cycle 1 (21 days)
Title
Objective response rate (ORR)
Description
Proportion of participants who achieved PR or better during the study per RECIST 1.1 and iRECIST
Time Frame
7 months
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Participants who discontinue treatment without disease progression
Time Frame
Up to 12 months
Title
Overall survival (OS)
Description
Date of study drug to date of death due to any cause
Time Frame
Up to 2 years from start of study drug
Title
Duration of treatment (DoT)
Description
Disease response for time of duration on treatment
Time Frame
7 months
Title
Disease control rate (DCR)
Description
Percentage of patients who have achieved CR, PR and stable disease
Time Frame
7 months
Title
Duration of response (DoR)
Description
Time from documentation of tumor response to disease progression per RECIST and iRECIST 1.1
Time Frame
Up to 12 months
Title
PK of grapiprant: AUC
Description
Area under the plasma concentration-time curve
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
PK of grapiprant: Cmax
Description
Peak serum concentration of grapiprant
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
Plasma decay half-life (t1/2)
Description
Measurement of half-life of grapiprant after dosing
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
Apparent oral clearance (CL/F)
Description
Rate of elimination of the drug from plasma after oral administration
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
Peak to trough ratio
Description
Measure how drug effect is sustained over dose interval
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
Observed accumulation ratio
Description
Relationship between the dosing interval and the rate of elimination for the drug
Time Frame
Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with Cycle 4 (every 42 days) through end of treatment (average of 4 months).
Title
Pharmacodynamic immune effects in paired tumor biopsies
Description
Asses changes in tumor infiltrating helper T cells, cytoxic T cells and regulatory monocyte/macrophages with study treatment
Time Frame
Predose through cycle 3 (each cycle is 21 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male and female adult patients at least 18 years of age on day of signing informed consent
Histologically confirmed non-small cell lung cancer (NSCLC) adenocarcinoma
Advanced (stage IIIb) disease that is not amenable to curative intent treatment with concurrent chemoradiation and metastatic (stage IV) patients
Progressed clinically and/or radiographically per RECIST v1.1 after receiving a PD-1 or PD-L1 antagonist for a minimum of 12 weeks
Measurable disease per RECIST v1.1
Disease that can be safely accessed via bronchoscopic, thoracoscopic or percutaneous biopsy for multiple core biopsies and participant is willing to provide tissue from newly obtain biopsies on study in a subgroup of patients
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Adequate organ function
Highly effective birth control
Able to swallow and absorb oral tablets
Key Exclusion Criteria:
Current use of NSAIDs, COX-2 inhibitors
Known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS gene alteration
No history of smoking (≤100 cigarettes lifetime)
History of severe hypersensitivity reactions to a PD-1/L1 antibody
Received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment or 5 half-lives, whichever is shorter
Received prior radiotherapy within 2 weeks of start of study treatment
Has received a live vaccine within 30 days prior to the first dose of study treatment
Taking strong CYP3A4 or P-glycoprotein inhibitors or inducers
Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
Known additional malignancy that is progressing or has required active treatment within the past 3 years (with some permitted exceptions)
Known active CNS metastases and/or carcinomatous meningitis
Active autoimmune disease that has required systemic treatment in past 2 years
History of pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Recent or current GI ulcer, colitis or non-immune colitis
Known history of human immunodeficiency virus (HIV) infection, or known active Hepatitis B, or Hepatitis C virus infection
Has had an allogeneic tissue/solid organ transplant
Clinically significant (i.e.active) cardiovascular disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Sager, MD
Organizational Affiliation
Arrys Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
START Midwest
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Facility Name
University of Pennsylvania Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Grapiprant (ARY-007) and Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 NSCLC Adenocarcinoma
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